This invention is in the fields of biochemistry, pharmacology, and anti-viral agents.
There is a major need for methods to prevent the spread of viral diseases that are transmitted through sexual contact, including genital herpes, which is caused by a virus called herpes simplex virus type 2 (HSV-2). A second herpes virus called herpes simplex virus type 1 (HSV-1) is occasionally detected in genital lesions, but it is usually associated with cold sores around the mouth.
Herpes simplex viruses are complex by viral standards. They carry roughly 70,000 base pairs of double-stranded DNA, and more than 50 open reading frame sequences that can encode polypeptides have been identified in their genomes. The DNA is enclosed within a capsid made of protein molecules, and the capsid is enclosed within an envelope made of a lipid bilayer. Protein molecules that help the virus bind to and infect certain types of cells project outwardly from the outer surface of the envelope. Those protein molecules are glycosylated, i.e., sugar molecules are attached to them, which makes it more difficult for an infected animal to generate an effective immune response to the virus. For more information on herpes viruses, see, e.g., Mindel 1989, Rapp 1984, Mertz 1990, and Kono and Nakajima 1985 (complete citations to books and articles are contained below, before the claims). Mindel 1989 offers a good introduction and overview.
Once contracted, genital herpes is incurable, and in addition to causing recurrent painful lesions, it poses a serious health threat. It can cause malignant transformation in animal and human cells, and has been linked to increased risks of cervical and vulvar cancer in women. The virus can also infect babies during birth, causing neonatal herpes, which is often fatal and can cause blindness, retardation, and other severe and permanent health problems if the baby survives.
Genital herpes is also believed to play an important role in the transmission of other sexually transmitted viruses, including acquired immunodeficiency syndrome (AIDS, which is caused by the human immunodeficiency virus, HIV). In effect, herpes lesions act as wounds or breaches in the protective layers of the skin and mucosal membranes. As an epidermal cell approaches the surface, it becomes squamous (flattened) and loses its chromosomes; its amino acids and nucleotides (the building blocks of proteins, DNA, and RNA) are depleted, and it becomes relatively inert metabolically. Within a few days after an epidermal cell reaches the surface, it is sloughed off, in a process of continuous replacement as other cells from the lower layers of the epidermis approach the surface. If a virus injects DNA or RNA into an epidermal cell in the outer layer of an intact and healthy region of the epidermis, the virus is not likely to be able to replicate inside the cell, since the cell will normally be depleted of the nucleotides and amino acids the virus needs. Therefore, a healthy and intact epidermal layer provides a major barrier against viral infection, but that barrier is breached by herpes lesions, which provide vulnerable entry sites for invading viruses. If someone with genital herpes has intercourse with someone else who has HIV or some other sexually transmitted virus, the person with herpes is more likely than a non-herpetic would be to contract AIDS or another disease as a result. In addition, in people infected with both herpes and the HIV virus (as is the case with many prostitutes), herpes lesions presumably can increase the number of infectious HIV viral particles emitted by the infected person, since white blood cells infected by the HIV virus are likely to be present in the fluid in the herpes lesions, trying to fight the herpes virus. Therefore, any method for preventing the spread of genital herpes can help slow down the spread of AIDS and other sexually transmitted viruses.
The need for ways to reduce the spread of herpes and AIDS are especially acute in view of the severe difficulties that have been encountered in trying to develop vaccines that can prevent infection by either virus. Despite intensive effort, there has been little progress in developing successful and effective vaccines against either virus.
The most widely recommended protective measure to prevent the spread of herpes, AIDS, and other sexually transmitted viruses (including papilloma, hepatitis, and Epstein-Barr viruses) requires the use of a condom during intercourse. However, even though numerous health care professionals, government officials, and the scientific, medical, and mass media have repeatedly urged all sexually active non-monogamous people to use condoms, many people at risk either fail or refuse to follow that advice.
Therefore, there is an urgent need for additional ways to reduce the spread of sexually transmitted viral diseases. As used herein, the term "anti-viral" is used broadly, to refer to an agent or method which can inhibit the replication or emission of viruses, or which can reduce the likelihood that a person or animal exposed to potentially infective viral particles will contract the viral disease, regardless of which stage or step of the viral cycle or transmission process is inhibited.